Towards understanding of stepwise acid-base dissociation in systems inclined to tautomerism: Nitro derivatives of fluorescein in dimethyl sulfoxide

Abstract

Understanding the dissociation of polyprotic acids in solution is important for many branches of chemistry and related sciences. A most important and at the same time knotty problem is the relation between the values of the stepwise dissociation constants. Sometimes even in a series of compounds that belong to the same family, the ratio of these constants varies in a wide range. This paper is aimed at disclosing the (unusual) relations between the first and second dissociation constants of the nitro derivatives of fluorescein in dimethyl sulfoxide. Some of the compounds were synthesized for the first time and characterized. The thermodynamic pKa values for 8 dyes were determined using the spectrophotometric method in buffer solutions and compared with the data for 12 earlier examined compounds; the Ka1/Ka2 ratio varies within an extremely wide range of 0.2 to 4 × 107. It is demonstrated that the peculiarities of the tautomerism of molecules, single-, and double-charged anions play a decisive role in this case. Neutral species, H2R, are represented by the quinonoid and lactonic tautomers. The fraction of the latter is higher for all the dyes with the free carboxylic group. For the single-charged anions, HR–, of the 4′- and 5′-mononitrofluoresceins, i.e., dyes with the NO2 group in the phthalic acid residue, the carboxylic group is dissociated (COO–) while the OH group not. In contrast, for the dyes bearing the NO2 group in the 4,5-; 4,5,4′-; 4,5,5′-; or 2,4,5,7-positions the HR– ions exist mainly as a tautomer with the dissociated hydroxyl group (O–) and un-dissociated COOH group. To the dianions, R2–, of fluorescein dyes a structure with the COO– and O– groups is normally ascribed. However, for the 4,5-dinitro-2,7-dibromofluorescein in DMSO, the fraction of the dianion existing as a lactonic tautomer is substantial; previously, it was shown that this tautomer of the R2– ion predominates for the 2,4,5,7-tetranitrofluorescein, 2,4,5,7,4′-, and 2,4,5,7,5′-pentanitrofluoresceins. After assessing the tautomeric relationships and singling out the so-called microscopic constants, the order of dissociating functional groups and the influence of the substituents in the xanthenes moiety became easy to understand. The values for the microscopic dissociation constants were confirmed by the pKa s of the model compounds with blocked carboxylic groups, COOCH3 or COOC2H5.